Periosteal reaction is frequently the first sign of systemic disease affecting the skeleton, including generalized osteopathia. It can be generalized, focal, monostotic or polyostotic and shows solid, lamellary or interrrupted spiculae-like reaction. A reliable diagnosis is possible from the interpretation of these changes, as for instance with spiculae: Very dense and evenly arranged spiculae are only seen in hemolytic anemias and metastases of neurogenic tumors. Onionskin like periosteal reaction with simultaneous transformation of the diaphyseal cortex are difficult to interpret. However, in case of hyperparathyreoidism, subperiosteal resorption and transformation of the diaphyseal cortex permit precise diagnosis. Follow-up examinations have prognostic and therapeutic value. The knowledge of the different morphology of periosteal reaction associated with systemic disease (including generalized osteopathias) is important in diagnostic radiology.